[unreadable] ECDI-coupled cell tolerance renders CD4+ T cells unresponsive to antigen-specific stimulation and has been used to inhibit and to prevent several animal models of autoimmune disorders. Preliminary data indicates that the same method used to tolerize CD4+ T cells renders CD8+ T cells unresponsive to subsequent stimulation as well. This treatment dramatically reduced CD8+ T cell effector function as well as altered viral clearance and susceptibility to demyelinating disease in mice infected with Theiler's murine encephalomyelitis virus (TMEV), a model of human multiple sclerosis. The tolerance of CD8+ T cells has potential applications for both the study of specific populations of cells in various infections and diseases as well as potential for immuno-therapy in autoimmune diseases in which CD8+ T cells mediate damage. Therefore, it is essential that the mechanisms of tolerance of CD8+ T cells be elucidated. The overall goal of this research proposal is to explore the functions of CD8+ T cells and the effects that ECDI-coupled cell tolerance has on their roles in both viral clearance and CD8+ T cell-mediated CNS autoimmune disease. [unreadable] [unreadable]